Method for producing A-hydroxyisobutyric acid amide and reactor

ABSTRACT

The present invention provides a method for producing α-hydroxyisobutyric acid amide by hydration of acetone cyanohydrin under the presence of a catalyst composed mainly of manganese oxide using a reactor in which at least two reaction regions are connected in series, the method being characterized by comprising: a step (B) of cyclically supplying at least a portion of a reaction liquid withdrawn from at least one reaction region to a first reaction region (I) in the reactor; and a step (b1) of further cyclically supplying at least a portion of the reaction liquid withdrawn from at least one reaction region to at least one reaction region other than the first reaction region. The method is also characterized in that an oxidizing agent is supplied to at least one reaction region in the reactor.

TECHNICAL FIELD

The present invention relates to a method for industrially producing anα-hydroxyisobutyric acid amide by hydration of an acetone cyanohydrinand a reaction apparatus. The α-hydroxyisobutyric acid amide is animportant compound as a raw material for the production of correspondinghydroxy carboxylic acid ester or unsaturated carboxylic acid ester, andthe development of a method for industrially stably producing anα-hydroxyisobutyric acid amide has great significance.

BACKGROUND ART

Various methods for producing an α-hydroxyisobutyric acid amide byhydration of an acetone cyanohydrin in the presence of a catalystcomposed mainly of manganese oxide have been disclosed. For example,Patent Document 1 discloses that in hydration of an acetone cyanohydrinusing manganese oxide, reaction results are improved by adding acetoneto a reaction raw material consisting of acetone cyanohydrin and water,and that in this case, the conversion of acetone cyanohydrin is 99.0%and the yield of α-hydroxyisobutyric acid amide is 95%. However,according to the method described in Patent Document 1, the catalystlife is not sufficiently improved, and it is difficult to carry out themethod at large-scale commercial plants.

Several improved methods relative to the method described in PatentDocument 1 have been proposed. For example, a method in which anoxidizing agent such as oxygen and ozone is allowed to coexist (PatentDocument 2), a method in which pH of a reaction raw material is adjusted(Patent Documents 3 and 4), a method in which a portion of a reactionproduct liquid is circulated in order to adjust pH of a reaction rawmaterial (Patent Document 3), a method in which carbon dioxide isallowed to coexist (Patent Document 5), a method in which a catalyst ispretreated with a reduction solution prior to the reaction (PatentDocument 6), and a method in which the reaction is performed underreduced pressure (Patent Document 7) are disclosed.

These methods respectively exert effects of improving catalytic activityor catalyst life, but it is difficult to stably maintain a high acetonecyanohydrin conversion for a long period of time using a reaction rawmaterial containing an acetone cyanohydrin at a concentration of 30% byweight or more. For example, Patent Document 4 describes a workingexample in which a method of adjusting pH of a reaction raw material wascombined with a method of allowing an oxidizing agent to coexist and areaction raw material containing an acetone cyanohydrin at aconcentration of 30.4% by weight was used, but the life defined as thetime for the conversion to be reduced to less than 50% of that at thestart is not more than 58 days.

Further, Patent Documents 8 and 9 disclose a method in which, even whenthe conversion of acetone cyanohydrin is low, unreacted acetonecyanohydrin in a reaction product liquid is thermally decomposed intoacetone and hydrocyanic acid, and these substances are separated fromthe reaction product liquid and collected, and then acetone cyanohydrinis made therefrom again. However, this method is not economical becauseextra energy is required for a thermal decomposition reaction and anacetone cyanohydrin synthesis reaction.

PRIOR ART DOCUMENTS Patent Documents

-   Patent Document 1: Japanese Laid-Open Patent Publication No. S52-222-   Patent Document 2: Japanese Laid-Open Patent Publication No.    H03-188054-   Patent Document 3: Japanese Laid-Open Patent Publication No.    H02-196763-   Patent Document 4: Japanese National-phase PCT Laid-Open Patent    Publication No. 2010-510276-   Patent Document 5: Japanese Laid-Open Patent Publication No.    1107-076563-   Patent Document 6: Japanese Laid-Open Patent Publication No.    H02-298718-   Patent Document 7: Japanese Laid-Open Patent Publication No.    H04-149164-   Patent Document 8: Japanese Laid-Open Patent Publication No.    H06-172283-   Patent Document 9: Japanese Laid-Open Patent Publication No.    H06-184072

SUMMARY OF THE INVENTION Problems to be Solved by the Invention

In general, synthesis of an acetone cyanohydrin by a reaction betweenhydrocyanic acid and acetone quantitatively proceeds in the presence ofan alkali catalyst, and therefore, an acetone cyanohydrin at a highconcentration of 50% by weight or more can be easily obtained. However,when hydration is performed using a reaction raw material containing anacetone cyanohydrin at a high concentration in the presence of acatalyst composed mainly of manganese oxide, the catalytic activity israpidly reduced. For this reason, it is general to use alow-concentrated acetone cyanohydrin as a raw material. However, when alow-concentrated acetone cyanohydrin is used, the concentration ofα-hydroxyisobutyric acid amide in a reaction product liquid obtained isalso low, and a large amount of energy is consumed in theconcentration/purification process.

The problem to be solved by the present invention is to provide a methodfor producing an α-hydroxyisobutyric acid amide by hydration of anacetone cyanohydrin in the presence of a catalyst composed mainly ofmanganese oxide, wherein the conversion of acetone cyanohydrin can bestably maintained at a high level for a long period of time even undersevere conditions in which the α-hydroxyisobutyric acid amide issynthesized from a reaction raw material containing an acetonecyanohydrin at a concentration of 30% by weight or more.

Means for Solving the Problems

The present inventors diligently made researches in order to solve theabove-described problem, and found that the reduction in the catalyticactivity is mainly caused by elution of manganese as the main componentof the catalyst and that the elution amount of manganese is closelyrelated to the acetone cyanohydrin concentration in the reaction liquid.Further, the present inventors found that, according to thebelow-described present invention, the acetone cyanohydrin concentrationin each reaction region can be decreased, the catalyst life can beimproved, and the conversion of acetone cyanohydrin can be maintained ata high level for a significantly longer period of time and more stablycompared to the prior art even under severe conditions in which theα-hydroxyisobutyric acid amide is synthesized from a reaction rawmaterial containing an acetone cyanohydrin at a concentration of 30% byweight or more, and thus the present invention was achieved.

Specifically, the present invention is as follows:

<1> A method for producing α-hydroxyisobutyric acid amide by hydrationof acetone cyanohydrin in the presence of a catalyst composed mainly ofmanganese oxide using a reaction apparatus in which at least tworeaction regions are connected in series, wherein the method comprises:

a step (B) of cyclically supplying at least a portion of a reactionliquid withdrawn from at least one reaction region to a first reactionregion (I) in the reaction apparatus; and

a step (b1) of further cyclically supplying at least a portion of thereaction liquid withdrawn from at least one reaction region to at leastone reaction region other than the first reaction region, and wherein

an oxidizing agent is supplied to at least one reaction region in thereaction apparatus.

<2> A method for producing α-hydroxyisobutyric acid amide by hydrationof acetone cyanohydrin in the presence of a catalyst composed mainly ofmanganese oxide using a reaction apparatus in which at least tworeaction regions are connected in series, wherein the method comprises:

a step (A) of supplying a reaction raw material liquid containing theacetone cyanohydrin dividedly to a first reaction region (I) and atleast one reaction region other than the first reaction region in thereaction apparatus;

a step (B) of cyclically supplying at least a portion of a reactionliquid withdrawn from at least one reaction region to the first reactionregion (I) in the reaction apparatus; and

a step (b1) of further cyclically supplying at least a portion of thereaction liquid withdrawn from at least one reaction region to at leastone reaction region other than the first reaction region, and wherein

an oxidizing agent is supplied to at least one reaction region in thereaction apparatus.

<3> The method for producing α-hydroxyisobutyric acid amide according toitem <1> or <2>, wherein at least a part of the step (b1) is conductedat a position nearer to an outlet of the reaction apparatus compared toa reaction region that is nearest to an inlet of the reaction apparatusamong at least one reaction region from which the reaction liquid iswithdrawn in order to cyclically supply the reaction liquid to the firstreaction region (I).

<4> The method for producing α-hydroxyisobutyric acid amide according toitem <3>, wherein at least a part of the step (b1) is conducted at aposition nearer to the outlet of the reaction apparatus compared toevery reaction region from which the reaction liquid is withdrawn inorder to cyclically supply the reaction liquid to the first reactionregion (I).

<5> The method for producing α-hydroxyisobutyric acid amide according toany one of items <1> to <4>, wherein in the step (b1), said at least onereaction region other than the first reaction region is identical tosaid at least one reaction region.

<6> The method for producing α-hydroxyisobutyric acid amide according toany one of items <1> to <5>, wherein the number of the reaction regionsconnected in series is 7 or less.

<7> The method for producing α-hydroxyisobutyric acid amide according toitem <2>, wherein the number of the reaction regions to which thereaction raw material liquid containing the acetone cyanohydrin issupplied in the step (A) is 5 or less.

<8> The method for producing α-hydroxyisobutyric acid amide according toitem <1>, wherein the method comprises a step of supplying a reactionraw material liquid containing the acetone cyanohydrin, and wherein theratio of the acetone cyanohydrin in the total amount of the reaction rawmaterial liquid is 30% by weight or more.

<9> The method for producing α-hydroxyisobutyric acid amide according toitem <2>, wherein the ratio of the acetone cyanohydrin in the totalamount of the reaction raw material liquid is 30% by weight or more.

<10> The method for producing α-hydroxyisobutyric acid amide accordingto any one of items <1> to <9>, wherein the ratio of the acetonecyanohydrin in the total amount of a reaction region supply liquid (C)to be supplied to said at least two reaction regions is 25% by weight orless, and wherein the reaction region supply liquid (C) is supplied toeach of the reaction regions and is at least one selected from the groupconsisting of the reaction raw material liquid, a diluent, and areaction liquid flowing out or withdrawn from the reaction regions.

<11> The method for producing α-hydroxyisobutyric acid amide accordingto any one of items <1> to <10>, wherein an oxygen-containing gas isused as the oxidizing agent, and wherein the oxygen concentration in theoxygen-containing gas is 2 to 50% by volume.

<12> The method for producing α-hydroxyisobutyric acid amide accordingto item <11>, wherein the gas in the reaction region is exchanged bysupplying a gas having a sufficient oxygen concentration whilewithdrawing a gas having a reduced oxygen concentration.

<13> The method for producing α-hydroxyisobutyric acid amide accordingto any one of items <1> to <12>, wherein the catalyst composed mainly ofmanganese oxide is manganese dioxide.

<14> The method for producing α-hydroxyisobutyric acid amide accordingto any one of items <1> to <13>, wherein the catalyst composed mainly ofmanganese oxide comprises a compound represented by composition formula:Mn_(a)K_(b)M_(c)O_(d)

wherein: Mn represents manganese; K represents potassium; O representsoxygen; M represents at least one element selected from V, Sn and Bi;and regarding the atomic ratio of each element, when a=1, b is 0.005 to0.5, c is 0.001 to 0.1, and d is 1.7 to 2.0.

<15> A reaction apparatus for producing α-hydroxyisobutyric acid amideby hydration of acetone cyanohydrin in the presence of a catalystcomposed mainly of manganese oxide, wherein the reaction apparatus hasat least two reaction regions connected in series and further has:

-   (a) a piping for supplying a reaction raw material liquid containing    the acetone cyanohydrin dividedly to a first reaction region (I) and    at least one reaction region other than the first reaction region in    the reaction apparatus; and/or-   (b) a piping for cyclically supplying at least a portion of a    reaction liquid withdrawn from at least one reaction region to the    first reaction region (I) in the reaction apparatus,-   and wherein the reaction apparatus further has a piping for    supplying an oxidizing agent to at least one reaction region.

<16> The reaction apparatus according to item <15>, further having apiping for cyclically supplying at least a portion of the reactionliquid withdrawn from at least one reaction region to at least onereaction region other than the first reaction region.

<17> The reaction apparatus according to item <16>, which has at leastone circulation loop composed of: at least one reaction region otherthan the first reaction region; at least one reaction region from whichthe reaction liquid is withdrawn in order to cyclically supply thereaction liquid to said reaction region; and a piping for connecting theformer reaction region and the latter reaction region, wherein both theat least one reaction region other than the first reaction region andthe at least one reaction region from which the reaction liquid iswithdrawn, which constitute at least one circulation loop (V) among saidcirculation loop, are placed at a position nearer to an outlet of thereaction apparatus compared to a reaction region that is nearest to aninlet of the reaction apparatus among at least one reaction region fromwhich the reaction liquid is withdrawn in order to cyclically supply thereaction liquid to the first reaction region (I).

<18> The reaction apparatus according to item <17>, wherein both the atleast one reaction region other than the first reaction region and theat least one reaction region from which the reaction liquid iswithdrawn, which constitute the circulation loop (V), are placed at aposition nearer to the outlet of the reaction apparatus compared toevery reaction region from which the reaction liquid is withdrawn inorder to cyclically supply the reaction liquid to the first reactionregion (I).

<19> The reaction apparatus according to any one of items <15> to <18>,wherein an equipment for withdrawing the oxidizing agent is connected tothe first reaction region (I) and/or a position between at least onereaction region other than the first reaction region and anotherreaction region, or the first reaction region (I) and/or the middleportion of at least one reaction region other than the first reactionregion.

Advantageous Effect of the Invention

According to the present invention, when producing anα-hydroxyisobutyric acid amide by hydration of an acetone cyanohydrin inthe presence of a catalyst composed mainly of manganese oxide, theconversion of acetone cyanohydrin can be maintained at a high level fora significantly longer period of time and more stably compared to theprior art even under severe conditions in which the α-hydroxyisobutyricacid amide is synthesized from a reaction raw material containing anacetone cyanohydrin at a concentration of 30% by weight or more.Therefore, the present invention has great industrial significance.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a process flow diagram showing an example of the reactionapparatus of the present invention which dividedly supplies ACH (acetonecyanohydrin) and cyclically supplies a reaction liquid.

FIG. 2 is a process flow diagram showing another example of the reactionapparatus of the present invention which dividedly supplies ACH andcyclically supplies a reaction liquid (a system in which a plurality ofreaction regions are provided in a reactor).

FIG. 3 is a process flow diagram showing another example of the reactionapparatus of the present invention which dividedly supplies ACH andcyclically supplies a reaction liquid (a system in which the temperatureof the reaction liquid withdrawn is adjusted using a heat exchanger andthen the reaction liquid is returned to the original reaction region).

FIG. 4 is a process flow diagram showing another example of the reactionapparatus of the present invention which dividedly supplies ACH andcyclically supplies a reaction liquid (a system in which a circulatingliquid is returned to a plurality of reaction regions).

FIG. 5 is a process flow diagram showing the reaction apparatus ofExample 1.

FIG. 6 is a process flow diagram showing the reaction apparatus ofExample 3.

EMBODIMENTS FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described in detail.

The reaction apparatus of the present invention, which can be used forthe production of an α-hydroxyisobutyric acid amide (hereinafterreferred to as HBD in principle), is a reaction apparatus in which atleast two reaction regions are connected in series. In this regard, thereaction region refers to an independent section in which a catalystcomposed mainly of manganese oxide, which has catalytic activity inhydration of an acetone cyanohydrin (hereinafter referred to as ACH inprinciple), exists. In this reaction region, ACH reacts with water andis converted to HBD that is an objective substance. This reaction regionmay be a reactor filled with the catalyst composed mainly of manganeseoxide, or may be each of several catalyst zones (catalyst layers)separately provided in one reactor.

In the method for producing HBD of the present invention, the number ofreaction regions connected in series is not particularly limited as longas it is 2 or more. However, when there are too many reaction regionsconnected in series, the apparatus becomes complicated and it becomescomplicated to control a reaction in each of the reaction regions.Therefore, from a practical viewpoint, the number of the reactionregions connected in series is preferably 2 to 7, and particularlypreferably 3 to 5. Further, the upper limit of the total number ofreaction regions is not particularly limited. Moreover, a reactionregion, which has a parallel relationship with the reaction regionsconnected in series, may exist.

In the method for producing HBD of the present invention, the reactionraw material liquid refers to an ACH-containing raw material liquidsupplied to the reaction regions in the reaction apparatus via a supplyline of reaction raw material liquid. That is, ACH is supplied to thereaction regions via the supply line of reaction raw material liquid asthe reaction raw material liquid. The HBD concentration in the reactionproduct liquid flowing out from the last reaction region is determinedby the ACH concentration in the reaction raw material liquid and theconversion of hydration. When the aforementioned HBD concentration islow, a large amount of energy is consumed in processes of condensationand purification, resulting in increase in the HBD purification cost.From the viewpoint of the above-described HBD purification cost, it ispreferred to employ a high ACH concentration in the reaction rawmaterial liquid. As described later, in the case of supplying thereaction raw material liquid dividedly to a plurality of reactionregions, the reaction raw material liquid is supplied via a plurality ofsupply lines of reaction raw material liquid. The ACH concentration inthe reaction raw material liquid supplied to a plurality of reactionregions may vary.

In general, an ACH synthesis reaction using hydrocyanic acid and acetoneas raw materials quantitatively proceeds in the presence of an alkalicatalyst, and ACH is obtained at a concentration of 50% by weight ormore. In the method for producing HBD of the present invention, as thereaction raw material liquid containing ACH to be used in the HBDproduction, a reaction liquid containing ACH at a high concentrationobtained by the above-described ACH synthesis reaction may be used.Alternatively, a liquid obtained by mixing a diluent with the reactionliquid containing ACH at a high concentration obtained by theabove-described ACH synthesis reaction may be used as the reaction rawmaterial liquid containing ACH. Specifically, the ACH concentration inthe reaction raw material liquid to be used in the HBD production may beadjusted to the above-described predetermined concentration using adiluent according to need. Like the prior art, as the diluent, an excessamount of water, which is a raw material for hydration, may be used, andacetone, which h functions to suppress an ACH decomposition reactionthat is a side reaction, may also be used. Other than water and acetone,amides such as formamide, dimethylformamide, dimethylacetamide and HBDthat is a reaction product can also be used as the diluent. As thediluent, the above-described compounds may be used solely, or two ormore of them may be used in combination. Among them, as the diluent,water, acetone, HBD and formamide are preferred, and among amides, HBDis particularly preferred. In the present invention, it is defined thatthe reaction liquid flowing out or withdrawn from the reaction region isnot included in the diluent, because it contains a certain quantity ofunreacted ACH.

In the case of using the liquid obtained by mixing the diluent with thereaction liquid containing ACH at a high concentration obtained by theACH synthesis reaction as the reaction raw material liquid containingACH, the timing and method of mixing the diluent are not particularlylimited. For example, the reaction raw material liquid containing ACHcan be obtained by a method in which the reaction liquid containing ACHat a high concentration is mixed with the diluent in a storage tank tobe diluted to have a desired ACH concentration. Further, it is alsopossible to obtain the reaction raw material liquid containing ACH byjoining the reaction liquid containing ACH at a high concentrationobtained by the ACH synthesis into a supply line of diluent immediatelyprior to be directly supplied to any of reaction regions.

In the present invention, when the reaction raw material liquidcontaining ACH is obtained by mixing the reaction liquid containing ACHat a high concentration obtained by the ACH synthesis reaction with thediluent, it is defined that the ratio of ACH in the total amount of thereaction raw material liquid refers to the weight fraction of ACHrelative to the total weight of the reaction liquid containing ACH at ahigh concentration obtained by the ACH synthesis reaction and thediluent.

Further, when the reaction liquid containing ACH at a high concentrationobtained by the ACH synthesis reaction is used as the reaction rawmaterial liquid, it is defined that the ratio of ACH in the total amountof the reaction raw material liquid refers to the weight fraction of ACHrelative to the total weight of the reaction liquid.

As described above, in the method for producing HBD of the presentinvention, the reaction raw material liquid may be supplied dividedly toa plurality of reaction regions. Further, the ACH concentration in thereaction raw material liquid supplied to the respective reaction regionsmay be the same or may vary. When the reaction raw material liquid issupplied to a plurality of reaction regions, the ratio of ACH in thetotal amount of the reaction raw material liquid refers to the ratio(weight fraction) of the total weight of ACH contained in the reactionraw material liquid supplied to the respective reaction regions in thetotal weight of the reaction raw material liquid supplied to therespective reaction regions.

The ratio of ACH in the total amount of the reaction raw material liquidis preferably 30% by weight or more, more preferably 30% by weight to83% by weight, and most preferably 35% by weight to 53% by weight.

In the HBD production of the present invention, as described above, theratio of ACH in the total weight of the reaction raw material liquid tobe used in the HBD production is preferably 30% by weight or more, butthe ACH concentration in the below-described reaction region supplyliquid (C) is lower than the ACH concentration in the reaction rawmaterial liquid. The reaction region supply liquid (C) refers to aliquid to be supplied to each of the reaction regions and consists of atleast one selected from the reaction raw material liquid, the diluent,and the reaction liquid flowing out or withdrawn from the reactionregions. In the present invention, the ratio of the amount of ACH in thetotal amount of the reaction region supply liquid (C) is preferably 25%by weight or less. In this regard, the total amount of the reactionregion supply liquid (C) means the sum of the amounts of the reactionregion supply liquid (C) supplied to the respective reaction regions.Further, hydration is performed with the ACH concentration in thereaction region supply liquid (C) supplied to all the reaction regionsin the reaction apparatus being adjusted to preferably 25% by weight orless, more preferably 20% by weight or less, and particularly preferably15% by weight or less. This is because, by reduction in the ACHconcentration in the reaction liquid at the inlet of the reactionregion, not only an effect of simply reducing the reaction load of thecatalyst is exerted, but also a very important effect of reducingelution of manganese ion associated with the reaction is exerted. Elutedmanganese ion is precipitated on the surface of the catalyst positioneddownstream of the portion where manganese is eluted as a form of themanganese oxide or the manganese hydroxide that has low reactivity or noreactivity, and this may cause reduction in catalyst life. Further,precipitation of the eluted manganese ion may cause bonding of eachparticle of the catalyst together to interfere with the catalysisexchange work, or may cause a breakdown of a reaction product liquiddelivery pump or pump for the purification system or blocking of piping,resulting in the troubles of the plant operation.

In the method for producing HBD of the present invention, the period forperforming hydration with the ratio of the amount of ACH in the totalamount of the reaction region supply liquid (C) being adjusted to 25% byweight or less is not particularly limited, but it is preferably atleast a half or more of the entire period of hydration, and particularlypreferably 80% or more of the entire period of hydration.

Only by a simple dilution operation, it is impossible to obtain ahighly-concentrated HBD solution corresponding to the ACH concentrationof the reaction raw material liquid to be used in the HBD production,and it is required to perform an operation of cyclically supplying thereaction liquid, and it is preferred to further combine therewith anoperation of dividedly supplying ACH. Specifically, the method forproducing HBD of the present invention is carried out according to anyone of the below-described two embodiments:

-   [Embodiment 1]: cyclically supplying the reaction liquid-   [Embodiment 2]: cyclically supplying the reaction liquid and    dividedly supplying ACH-   Hereinafter, the respective embodiments will be described in detail.

The first embodiment of the method for producing HBD of the presentinvention (hereinafter referred to as “Embodiment 1” in principle) is amethod for producing an α-hydroxyisobutyric acid amide by hydration ofan acetone cyanohydrin in the presence of a catalyst composed mainly ofmanganese oxide using a reaction apparatus in which at least tworeaction regions are connected in series, wherein the method comprises:

a step (B) of cyclically supplying at least a portion of a reactionliquid withdrawn from at least one reaction region to a first reactionregion (I) in the reaction apparatus; and

a step (b1) of further cyclically supplying at least a portion of thereaction liquid withdrawn from at least one reaction region to at leastone reaction region other than the first reaction region, and wherein

an oxidizing agent is supplied to at least one reaction region in thereaction apparatus.

In Embodiment 1, at least a portion of the reaction liquid withdrawnfrom at least one reaction region is cyclically used. This makes itpossible to reduce the ACH concentration in the reaction region supplyliquid (C) supplied to the respective reaction regions to improve thecatalyst life and to inhibit the troubles of the plant operation, and atthe same time, the HBD concentration in the reaction liquid at theoutlet of the last reaction region can be increased. Moreover, cyclicaluse of the reaction liquid has the effect to adjust pH of the reactionregion supply liquid (C) supplied to the reaction regions to 4 or more,which is preferable from the viewpoint of the catalyst life, andtherefore, the catalyst life can be extended by dual effect, i.e., theeffect exerted by pH adjustment and the effect of suppressing elution ofmanganese by means of adjustment of the ACH concentration.

In the step (B), at least one reaction region from which the reactionliquid is withdrawn in order to cyclically supply at least a portion ofthe reaction liquid to the first reaction region (I) may be the firstreaction region itself or a reaction region at a position nearer to theoutlet of the reaction apparatus compared to the first reaction region(downstream). Specifically, it may be any reaction region in thereaction apparatus of the present invention as long as it does notinterrupt the step (b1). In the step (b1), at least one reaction regionfrom which the reaction liquid is withdrawn in order to cyclicallysupply at least a portion of the reaction liquid to at least onereaction region other than the first reaction region may be the at leastone reaction region other than the first reaction region itself to whichthe reaction liquid is cyclically supplied or a reaction region at aposition nearer to the outlet of the reaction apparatus compared to theat least one reaction region other than the first reaction region(downstream).

In the step (B), at least one reaction region from which the reactionliquid is withdrawn in order to cyclically supply at least a portion ofthe reaction liquid to the first reaction region (I) may be a pluralityof reaction regions. Further, in the step (b1), at least one reactionregion from which the reaction liquid is withdrawn in order tocyclically supply at least a portion of the reaction liquid to at leastone reaction region other than the first reaction region may be aplurality of reaction regions. The at least one reaction region fromwhich the reaction liquid is withdrawn to cyclically supply it in thestep (B) and the at least one reaction region from which the reactionliquid is withdrawn to cyclically supply it in the step (b1) may be thesame or different from each other, but preferably different from eachother.

In Embodiment 1, it is more preferred to cyclically supply the reactionliquid to at least one reaction region other than the first reactionregion in addition to the first reaction region (I) from the viewpointthat the ACH concentration in the reaction region supply liquid (C)supplied to the reaction regions can be more easily reduced, resultingin decrease in elution of manganese ion and that it is possible to buildan efficient process with a smaller number of reaction regions. When thereaction liquid is cyclically supplied to reaction regions other thanthe first reaction region, with respect to at least one reaction region,it is desirable that the reaction liquid is withdrawn from a reactionregion (named as the secondary opening for withdrawing the reactionliquid) provided at a position nearer to the outlet of the reactionapparatus (downstream) compared to a reaction region (named as theprimary opening for withdrawing the reaction liquid) from which thereaction liquid is withdrawn to cyclically supply it to the firstreaction region (I), and that the reaction liquid is supplied to anyreaction region provided at a position between the primary opening forwithdrawing the reaction liquid and the secondary opening forwithdrawing the reaction liquid or to the reaction region itself thatprovides the secondary opening for withdrawing the reaction liquid.

In Embodiment 1, it is possible to provide a plurality of primaryopenings for withdrawing the reaction liquid to the reaction apparatusand to cyclically supply the reaction liquid from a plurality ofreaction regions to the first reaction region (I). In this case, adesirable positional relationship between the plurality of primaryopenings for withdrawing the reaction liquid, reaction regions otherthan the first reaction region to which the reaction liquid iscyclically supplied and the secondary opening for withdrawing thereaction liquid is as described below. Specifically, in Embodiment 1, atleast one pair of the reaction regions other than the first reactionregion to which the reaction liquid is cyclically supplied and thesecondary opening for withdrawing the reaction liquid is desirablyprovided at a position nearer to the outlet of the reaction apparatus(downstream) compared to a primary opening for withdrawing the reactionliquid nearest to the inlet of the reaction apparatus among theplurality of primary openings for withdrawing the reaction liquidprovided. More desirably, it is provided at a position nearer to theoutlet of the reaction apparatus (downstream) compared to the firstprimary opening for withdrawing the reaction liquid in which theintegrated quantity of the reaction liquid withdrawn from each of theplurality of primary openings for withdrawing the reaction liquidprovided exceeds 50% of the total amount of the reaction liquidwithdrawn from all the plurality of primary openings for withdrawing thereaction liquid provided. Most desirably, at least one pair of thereaction regions other than the first reaction region to which thereaction liquid is cyclically supplied and the secondary opening forwithdrawing the reaction liquid is provided at a position nearer to theoutlet of the reaction apparatus (downstream) compared to all theprimary openings for withdrawing the reaction liquid. In this way, inaddition to a reaction liquid circulation pathway composed of the firstreaction region (I), the reaction regions from which the reaction liquidis withdrawn to cyclically supply it to the first reaction region (I)and a circulation line, another reaction liquid circulation pathway,which is independent to some extent, is provided at a position nearer tothe outlet of the reaction apparatus. In this case, reaction conditionsof reaction regions existing in the respective reaction liquidcirculation pathways can be independently controlled and optimized, andit is easier to maximize the performance of the filled catalyst.

In Embodiment 1, the ACH concentration in the reaction region supplyliquid (C) supplied to the reaction regions is adjusted by cyclicallysupplying the reaction liquid itself in which a compound having theelution effect such as water, acetone, HBD and formamide is contained,and therefore it is not necessary to additionally use a diluent.However, from a practical viewpoint, the ACH concentration in thereaction region supply liquid (C) supplied to the first reaction region(I) is preferably adjusted by using both a diluent and thecyclically-supplied reaction liquid. Other than water and acetone,amides such as formamide, dimethylformamide, dimethylacetamide and HBDthat is a reaction product can also be used as the diluent. As thediluent, the above-described compounds may be used solely, or two ormore of them may be used in combination. Among them, as the diluent,water, acetone, HBD and formamide are preferred, and among amides, HBDis particularly preferred.

The amount of the reaction liquid to be cyclically supplied is definedby the below-described formula (1) as the circulation ratio based on thesupply rate of the cyclically-supplied reaction liquid (X) and thesupply rate of the reaction region supply liquid (C) supplied to thereaction regions (Y):Circulation ratio=(X)/((Y)−(X))  formula (1)

The circulation ratio in Embodiment 1 is not particularly limited.

In Embodiment 1, the molar ratio between water and ACH in the reactionregion supply liquid (C) supplied to all the reaction regions in thereaction apparatus is not particularly limited, but the amount of wateris preferably 1 to 200 mol, and particularly preferably 10 to 100 molrelative to 1 mol of ACH. The molar ratio between acetone and ACH is notparticularly limited, but the amount of ACH is preferably 0.1 to 10 molrelative to 1 mol of acetone.

In Embodiment 1, the supply amounts of water and ACH contained in thereaction raw material liquid supplied to the reaction apparatus relativeto the total weight of the catalyst filled in all the reaction regionsin the reaction apparatus are not particularly limited, but in the caseof water, it is supplied preferably at a rate of 0.0625 to 0.625 g/hr,more preferably at a rate of 0.125 to 0.25 g/hr, and most preferably ata rate of 0.15 to 0.225 g/hr relative to 1 g of the catalyst. In thecase of ACH, it is supplied preferably at a rate of 0.05 to 0.5 g/hr,more preferably at a rate of 0.1 to 0.2 g/hr, and most preferably at arate of 0.12 to 0.18 g/hr relative to 1 g of the catalyst.

As the method for producing HBD of the present invention, thebelow-described second embodiment is particularly preferred. The secondembodiment of the method for producing HBD of the present invention is amethod for producing an α-hydroxyisobutyric acid amide by hydration ofan acetone cyanohydrin in the presence of a catalyst composed mainly ofmanganese oxide using a reaction apparatus in which at least tworeaction regions are connected in series, wherein the method comprises:

a step (A) of supplying a reaction raw material liquid containing theacetone cyanohydrin dividedly to a first reaction region (I) and atleast one reaction region other than the first reaction region in thereaction apparatus;

a step (B) of cyclically supplying at least a portion of a reactionliquid withdrawn from at least one reaction region to the first reactionregion (I) in the reaction apparatus; and

a step (b1) of further cyclically supplying at least a portion of thereaction liquid withdrawn from at least one reaction region to at leastone reaction region other than the first reaction region, and wherein

an oxidizing agent is supplied to at least one reaction region in thereaction apparatus.

In the above-described Embodiment 2, at least one reaction region otherthan the first reaction region in the step (A), i.e., at least onereaction region other than the first reaction region to which thereaction raw material liquid is dividedly supplied may be a plurality ofreaction regions. Further, at least one reaction region in the step(b1), i.e., at least one reaction region other than the first reactionregion to which at least a portion of the reaction liquid withdrawn fromat least one reaction region is cyclically supplied may be a pluralityof reaction regions. Moreover, the at least one reaction region otherthan the first reaction region in the step (A) and the at least onereaction region other than the first reaction region in the step (b1)may be the same or different from each other.

Specifically, it is particularly preferred to dividedly supply ACH inaddition to cyclically supplying at least a portion of the reactionliquid withdrawn from at least one reaction region as explained above.This is because, in addition to the above-described advantages ofEmbodiment 1, when compared to Embodiment 1, the ACH concentration inthe reaction region supply liquid (C) supplied to the respectivereaction regions can be decreased more efficiently, and the HBDconcentration in the reaction product liquid flowing out from the lastreaction region can be efficiently increased with a smaller number ofreaction regions, leading to building of a more efficient process.Hereinafter, the second embodiment of the method for producing HBD ofthe present invention (hereinafter sometimes referred to as “combinationmethod”) will be described in detail.

As the second embodiment, for example, when hydration of ACH is carriedout using a reaction apparatus in which three reaction regions areconnected in series, ACH can be dividedly supplied to the first reactionregion and the second reaction region. Alternatively, ACH can bedividedly supplied to the first reaction region and the third reactionregion. Alternatively, ACH can be dividedly supplied to all the threereaction regions.

Embodiment 2 has the following three advantages: the ACH concentrationin the reaction region supply liquid (C) supplied to the reactionregions can be easily decreased; the difference of the reaction loadbetween the respective reaction regions to which ACH is supplied can bedecreased; and the HBD concentration in the reaction liquid at theoutlet of the last reaction region can be maintained at a high leveleven when the ACH concentration in the reaction regions is low. Theseadvantages will be explained below.

Firstly, by reduction in the ACH concentration in the reaction regionsupply liquid (C) supplied to the reaction regions, not only an effectof simply reducing the reaction load of the catalyst, but also a veryimportant effect of reducing elution of manganese ion associated withthe reaction is exerted as described above. Specifically, by reducingthe ACH concentration in the reaction region supply liquid (C) suppliedto the reaction regions by means of dividedly supplying ACH, elution ofmanganese ion can be suppressed, the catalyst life can be improved, andthe number of the plant operation troubles can be decreased.

The second advantage will be explained below. As known well, in the caseof a simple continuous flow-type reaction in which a reaction rawmaterial is not dividedly supplied, the distance in which the reactionraw material is passed through catalyst-filled reaction regions is notdirectly proportional to the conversion, and a major part of thereaction is progressed at reaction regions in the former half throughwhich the reaction raw material is passed, and the ratio of the reactionprogressed at reaction regions in the latter half is small. Hydration ofACH is no exception. Therefore, by dividedly supplying ACH to two ormore reaction regions, the difference of the reaction load between therespective reaction regions can be reduced, and it can be expected thatthe catalyst life can be extended thereby.

The third advantage will be explained below. In the method of Embodiment2, after a portion of ACH in the first reaction region to which ACH issupplied becomes HBD, ACH is added to the second reaction region orlater. Therefore, the HBD concentration in the reaction liquid at theoutlet of each reaction region can be increased in a stepwise mannerwhile the ACH concentration in the reaction region supply liquid (C)supplied to the reaction regions is maintained at a low level. Forexample, when a reaction is performed using a reaction raw material withthe ACH concentration of 25% by weight in a one-pass reaction apparatusin which ACH is not dividedly supplied, even if the reaction iscompletely progressed, the HBD concentration in the reaction productliquid at the outlet of the last reaction region is no more than 30% byweight. Meanwhile, according to the above-described method for dividedlysupplying ACH, even when the ACH concentration in the reaction regionsupply liquid (C) supplied to all the reaction regions in the reactionapparatus is adjusted to 25% by weight or less, the HBD concentration inthe reaction product liquid flowing out from the last reaction regioncan be increased to, for example, 40% by weight or more. Therefore, thecost for separation of HBD from water, acetone or the like in thepurification system can be reduced, and it is very economical.

Thus, by dividedly supplying ACH, even when the ACH concentration in thereaction raw material liquid to be used in the HBD production is 30% byweight or more, the ACH concentration in the reaction region supplyliquid (C) supplied to the reaction regions can be reduced efficiently,and the difference of the reaction load between the respective reactionregions to which ACH is supplied can be decreased, and therefore thecatalyst life can be more extended compared to the conventional methods.Moreover, even when the ACH concentration in the reaction region supplyliquid (C) supplied to the reaction regions is low, the HBDconcentration in the reaction liquid flowing out from the last reactionregion, i.e., the reaction product liquid at the outlet of the reactionapparatus can be increased, and therefore it is more economical comparedto the conventional reaction processes.

In Embodiment 2, the number of reaction regions to which ACH isdividedly supplied is not particularly limited as long as it is 2 ormore. However, when there are too many reaction regions to which ACH isdividedly supplied, the apparatus becomes complicated and it becomescomplicated to control a reaction in each of the reaction regions.Therefore, from a practical viewpoint, the number of the reactionregions is preferably 2 to 5, and particularly preferably 3 to 4.

In Embodiment 2, the ACH distribution ratio (ACH division ratio) betweenthe reaction regions to which ACH is dividedly supplied is notparticularly limited, but it is preferred that the ratio of the amountof ACH supplied to the first reaction region relative to the totalamount of ACH supplied to the reaction apparatus is 50 to 98% by weight,and that the remaining ACH is dividedly supplied to the second reactionregion or later. This is because, since the reaction liquid iscyclically supplied to the first reaction region in Embodiment 2, evenwhen the amount of ACH dividedly supplied to the first reaction regionis increased, the ACH concentration can be reduced more easily comparedto the method of only dividedly supplying ACH, and in this way, the HBDconcentration in the reaction liquid at the outlet of the last reactionregion can be increased efficiently with a smaller number of reactionregions.

Also in Embodiment 2, it is more preferred to cyclically supply thereaction liquid to at least one reaction region other than the firstreaction region in addition to the first reaction region (I) from theviewpoint that the ACH concentration in the reaction region supplyliquid (C) supplied to the reaction regions can be more easily reduced,resulting in decrease in elution of manganese ion and that it ispossible to build an efficient process with a smaller number of reactionregions. Moreover, it is particularly preferred to cyclically supply thereaction liquid to the reaction regions to which ACH is dividedlysupplied. When the reaction liquid is cyclically supplied to reactionregions other than the first reaction region, it is desirable that theat least a portion of reaction liquid is withdrawn from a reactionregion (named as the secondary opening for withdrawing the reactionliquid) provided at a position nearer to the outlet of the reactionapparatus (downstream) compared to a reaction region (named as theprimary opening for withdrawing the reaction liquid) from which thereaction liquid is withdrawn to cyclically supply to the first reactionregion (I), and supplied to any reaction region provided at a positionbetween the primary opening for withdrawing the reaction liquid and thesecondary opening for withdrawing the reaction liquid or to the reactionregion itself that provides the secondary opening for withdrawing thereaction liquid.

In Embodiment 2, it is possible to provide a plurality of primaryopenings for withdrawing the reaction liquid to the reaction apparatusand to cyclically supply the reaction liquid from a plurality ofreaction regions to the first reaction region (I). In this case, adesirable positional relationship between the plurality of primaryopenings for withdrawing the reaction liquid, reaction regions otherthan the first reaction region to which the reaction liquid iscyclically supplied and the secondary opening for withdrawing thereaction liquid is as described below. Specifically, in Embodiment 2, atleast one pair of the reaction regions other than the first reactionregion to which the reaction liquid is cyclically supplied and thesecondary opening for withdrawing the reaction liquid is desirablyprovided at a position nearer to the outlet of the reaction apparatus(downstream) compared to a primary opening for withdrawing the reactionliquid nearest to the inlet of the reaction apparatus among theplurality of primary openings for withdrawing the reaction liquidprovided. More desirably, it is provided at a position nearer to theoutlet of the reaction apparatus (downstream) compared to the firstprimary opening for withdrawing the reaction liquid in which theintegrated quantity of the reaction liquid withdrawn from each of theplurality of primary openings for withdrawing the reaction liquidprovided exceeds 50% of the total amount of the reaction liquidwithdrawn from all the plurality of primary openings for withdrawing thereaction liquid provided. Most desirably, at least one pair of thereaction regions other than the first reaction region to which thereaction liquid is cyclically supplied and the secondary opening forwithdrawing the reaction liquid is provided at a position nearer to theoutlet of the reaction apparatus (downstream) compared to all theprimary openings for withdrawing the reaction liquid. In this way, inaddition to a reaction liquid circulation pathway composed of the firstreaction region (I), the reaction regions from which the reaction liquidis withdrawn to cyclically supply it to the first reaction region (I)and a circulation line, another reaction liquid circulation pathway,which is independent to some extent, is provided at a position nearer tothe outlet of the reaction apparatus. In this case, reaction conditionsof reaction regions existing in the respective reaction liquidcirculation pathways can be independently controlled and optimized, andit is easier to maximize the performance of the filled catalyst.

In Embodiment 2, the ACH concentration in the reaction region supplyliquid (C) supplied to the reaction regions is adjusted by cyclicallysupplying the reaction liquid itself in which a compound having theelution effect such as water, acetone, HBD and formamide is contained,and therefore it is not necessary to use the above-described diluent inaddition to the reaction liquid in order to adjust the ACHconcentration. However, from a practical viewpoint, the ACHconcentration in the reaction region supply liquid (C) supplied to thefirst reaction region (I) is preferably adjusted by using both thediluent and the cyclically-supplied reaction liquid because in this casethe circulation ratio explained later can be controlled within apreferred range. Other than water and acetone, amides such as formamide,dimethylformamide, dimethylacetamide and HBD that is a reaction productcan also be used as the diluent. As the diluent, the above-describedcompounds may be used solely, or two or more of them may be used incombination. Among them, as the diluent, water, acetone, HBD andformamide are preferred, and among amides, HBD is particularlypreferred.

In Embodiment 2, the molar ratio between water and ACH in the reactionregion supply liquid (C) supplied to all the reaction regions in thereaction apparatus is not particularly limited, but the amount of wateris preferably 1 to 200 mol, and particularly preferably 10 to 100 molrelative to 1 mol of ACH. The molar ratio between acetone and ACH is notparticularly limited, but the amount of ACH is preferably 0.1 to 10 molrelative to 1 mol of acetone.

In Embodiment 2, the total supply amounts of water and ACH contained inthe reaction raw material liquid supplied to the reaction apparatusrelative to the total weight of the catalyst filled in all the reactionregions in the reaction apparatus are not particularly limited, but inthe case of water, it is supplied preferably at a rate of 0.0625 to0.625 g/hr, more preferably at a rate of 0.125 to 0.25 g/hr, and mostpreferably at a rate of 0.15 to 0.225 g/hr relative to 1 g of thecatalyst. In the case of ACH, it is supplied preferably at a rate of0.05 to 0.5 g/hr, more preferably at a rate of 0.1 to 0.2 g/hr, and mostpreferably at a rate of 0.12 to 0.18 g/hr relative to 1 g of thecatalyst.

The amount of the reaction liquid to be cyclically supplied is definedby the below-described formula (1) as the circulation ratio based on thesupply rate of the cyclically-supplied reaction liquid (X) and thesupply rate of the reaction region supply liquid (C) supplied to thereaction regions (Y):Circulation ratio=(X)/((Y)−(X))  formula (1)

The circulation ratio in Embodiment 2 is not particularly limited, butwhen represented by the volume velocity ratio, it is preferably 0.5 to50, and particularly preferably 1 to 20. The circulation ratio is afactor which affects the ACH concentration in the reaction region supplyliquid (C) supplied to the reaction regions, and the larger thecirculation ratio is, the longer the catalyst life is. However, when theratio exceeds 50, the amount of the liquid passing through the reactionregions is increased, and this may lead to reduction in reactionperformance such as reduction in the conversion of ACH and increase inthe pressure loss.

Thus, in Embodiment 2, it is possible to increase the HBD concentrationin the reaction liquid at the outlet of the last reaction region moreefficiently with a smaller number of reaction regions compared to themethod in which only circulating supply of the reaction product liquidis performed (Embodiment 1), and therefore Embodiment 2 is the mosteconomical process.

Note that when the number of reaction regions is 3 or more, ACH may bedividedly supplied to the last reaction region as explained above, butit is preferred not to dividedly supply ACH to the last reaction region.This is because, when the number of reaction regions is 3 or more, amore efficient process can be obtained when dividedly supplying theentire ACH is finished at the reaction region that is next to the lastreaction region, the reaction is performed so that the ACH concentrationin the liquid at the inlet of the last reaction region becomes about 5%by weight, and the remaining ACH in an amount of about 5% by weight isconverted into HBD as much as possible in the last reaction region.Further, in Embodiment 1 and Embodiment 2, an embodiment in which areaction region is provided in the middle of a circulation line forcyclically supplying the reaction liquid is also included.

In the HBD production of the present invention, in all the reactionregions in the reaction apparatus, hydration of ACH is preferablyperformed in the presence of an oxidizing agent in order to prevent thecatalyst composed mainly of manganese oxide from being reduced anddeactivated. As a method for supplying the oxidizing agent for thispurpose, since the oxidizing agent is passed through the reactionapparatus together with the liquid, it is usually sufficient when theoxidizing agent is supplied to at least one reaction region in thereaction apparatus. For example, when the oxidizing agent is supplied tothe first reaction region, the oxidizing agent is passed through thesecond reaction region or later, and therefore, the oxidizing agent maybe supplied to the first reaction region. However, since the oxidizingagent is gradually consumed in the respective reaction regions, it isparticularly preferred to supply the oxidizing agent also to the secondreaction region or later depending on the oxidizing agent concentrationin the respective reaction regions. Specifically, in the HBD productionof the present invention, it is particularly preferred to supply theoxidizing agent to the first reaction region and at least one reactionregion other than the first reaction region. Obviously, the oxidizingagent may be supplied to all the reaction regions.

Examples of the oxidizing agent which can be used in the HBD productionof the present invention include: gases containing an oxygen atom suchas oxygen and ozone; peroxides such as hydrogen peroxide, sodiumperoxide, magnesium peroxide, benzoyl peroxide and diacetyl peroxide;peracids and persalts such as performic acid, peracetic acid andammonium persulfate; or oxyacids and oxoates such as periodic acid,perchloric acid, sodium periodate, iodic acid, bromic acid, potassiumchlorate and sodium hypochlorite. Among them, gases containing an oxygenatom such as oxygen and ozone are preferred, and oxygen is particularlypreferred. These oxidizing agents may be used solely, or two or more ofthem may be used in combination. Further, these oxidizing agents may bedissolved in the raw material or diluent to be supplied to the reactionregions, or may be supplied to the reaction regions in the form of gas.When represented by the molar ratio relative to the raw material ACH,the supply amount of these oxidizing agents is preferably 0.001 to 0.15,and particularly preferably 0.005 to 0.05.

When oxygen is used as the oxidizing agent, pure oxygen may be used, butusually, oxygen is used with dilution with an inert gas such as nitrogenand rare gas. It is also possible to use air directly or to mix air withoxygen or an inert gas to adjust the concentration for use. The oxygenconcentration in such an oxygen-containing gas is not particularlylimited, but it is preferably 2 to 50% by volume, and particularlypreferably 5 to 10% by volume.

When the oxygen-containing gas is used as the oxidizing agent, it ispreferred to use a so-called trickle-bed reactor, in which a catalyst isfilled as a fixed bed and a reaction liquid flows between a solid phaseand a gas phase. By using this, it is possible to carry out gooddispersion of the reaction liquid and gas and contact between thereaction liquid and the catalyst. Such a reaction method is called“trickle flow-type continuous reaction”. The flows of the reactionliquid and gas may be either countercurrent flow or co-current flow.

When the oxygen-containing gas is used as the oxidizing agent, since itmay be supplied from the inlet of the first reaction region in the caseof co-current flow, and from the outlet of the last reaction region inthe case of countercurrent flow, for the gas to be run through all thereaction regions, the oxygen-containing gas is preferably supplied tothe first or last reaction region. However, since oxygen is graduallyconsumed in the respective reaction regions, it is more preferred tosupply the oxygen-containing gas also to reaction regions other than thefirst or last reaction region depending on the oxygen concentration inthe respective reaction regions. In this case, it is particularlypreferred to exchange gas in the respective reaction regions bysupplying gas having a sufficient oxygen concentration while withdrawinggas whose oxygen concentration has decreased. In this regard, the oxygenconcentration of the gas whose oxygen concentration has decreased is notparticularly limited. For example, when using a gas containing oxygen ata concentration of 10%, it may be newly supplied while withdrawing a gaswhose oxygen concentration has decreased to about 5%. The speed forexchanging gas can be suitably determined depending on the oxygenconcentration in the respective reaction regions.

Specifically, when the oxygen-containing gas is run through byco-current flow, it is preferred to supply a gas having a sufficientoxygen concentration and withdraw a gas whose oxygen concentration hasdecreased in the first reaction region and at least one reaction regionother than the first reaction region. Obviously, supplying the gashaving a sufficient oxygen concentration and withdrawing the gas whoseoxygen concentration has decreased may be carried out in all thereaction regions. Meanwhile, when the oxygen-containing gas is runthrough by countercurrent flow, it is preferred to supply the gas havinga sufficient oxygen concentration and withdraw the gas whose oxygenconcentration has decreased in the last reaction region and at least onereaction region other than the last reaction region. Obviously,supplying the gas having a sufficient oxygen concentration andwithdrawing the gas whose oxygen concentration has decreased may becarried out in all the reaction regions.

The ratio of the gas which is withdrawn from the reaction regionsbecause of the reduction of the oxygen concentration is not particularlylimited. It is possible to withdraw the total amount of the gas to theoutside of the system, followed by supply of a new gas having asufficient oxygen content from a gas withdrawing point or theneighborhood thereof. It is also possible to withdraw only a portion ofthe gas passed through the catalyst region.

As the catalyst composed mainly of manganese oxide to be used in the HBDproduction of the present invention, manganese dioxide can be used. Ingeneral, manganese dioxide is a manganese oxide having a compositionformula of MnO_(1.7) to MnO₂, and various crystal structures thereofsuch as α-type, β-type, γ-type, δ-type and ε-type are known. Further,manganese dioxides in which an alkali metal element is included in acrystal structure (hereinafter referred to as “modified manganesedioxides”) are also known, and various crystal structures such as α-typeand δ-type of modified manganese dioxides are known. In the presentinvention, these manganese dioxides can be suitably used, but modifiedmanganese dioxides are more preferred, and modified manganese dioxideshaving an α-type structure are particularly preferred. The type of thealkali metal element included in modified manganese dioxides is notparticularly limited, but lithium, sodium and potassium are preferred.The amount of the alkali metal element included in modified manganesedioxides is not particularly limited, but when represented by the atomicratio of the alkali metal element relative to the manganese element,alkali metal element/manganese is preferably 0.005 to 0.5, andparticularly preferably 0.01 to 0.25.

Manganese dioxide naturally occurs, but when used as a catalyst, it isappropriate to use a manganese dioxide obtained by using a method inwhich a divalent manganese is oxidized to prepare manganese dioxide, ora method in which a heptavalent manganese is reduced to preparemanganese dioxide, or combination of these methods. Examples of suchmethods for producing manganese dioxide include a method in which apermanganate compound is reduced in a neutral or alkaline region at 20to 100° C. (Zeit. Anorg. Allg. Chem., 309, pp. 1-32 and 121-150,(1961)), a method in which an aqueous solution of potassium permanganateis reacted with an aqueous solution of manganese sulfate under acidicconditions (J. Chem. Soc., p. 2189, (1953); Japanese Laid-Open PatentPublication No. S51-71299), a method in which a permanganate is reducedwith a hydrohalogenic acid (Japanese Laid-Open Patent Publication No.S63-57535), a method in which a permanganate is reduced with apolyvalent carboxylic acid or polyhydric alcohol (Japanese Laid-OpenPatent Publication No. H09-24275, Japanese Laid-Open Patent PublicationNo. H09-19637), a method in which a permanganate is reduced withhydrazine, hydroxycarboxylic acid or a salt thereof (Japanese Laid-OpenPatent Publication No. H06-269666) and a method in which an aqueoussolution of manganese sulfate is subjected to electrolytic oxidation.

As the method for preparing the catalyst composed mainly of manganeseoxide in the present invention, the aforementioned various methods canbe used, but it is preferred to use a method in which a divalentmanganese compound and a heptavalent manganese compound aresimultaneously used from the viewpoint that the crystal form andspecific surface area of the modified manganese dioxide and the type andamount of the alkali metal element can be controlled thereby. As thedivalent manganese source to be used for preparing the catalyst,water-soluble compounds such as sulfates, nitrates and halides arepreferred, and among them, sulfates are particularly preferred.Meanwhile, as the heptavalent manganese source, permanganates of alkalimetal elements are preferred, and among them, lithium permanganate,sodium permanganate and potassium permanganate are particularlypreferred. As the alkali metal source, water-soluble compounds such assulfates, nitrates, bicarbonates and hydroxides can be used, butusually, it is particularly preferred to use the aforementionedpermanganates as the alkali metal source. Regarding liquid properties,the modified manganese dioxide can be prepared either under acidicconditions or under basic conditions, but the preparation under acidicconditions is particularly preferred. In the case of the preparationunder basic conditions, it is preferred to wash the modified manganesedioxide with an acidic solution such as dilute sulfuric acid before thereaction.

As the catalyst composed mainly of manganese oxide in the presentinvention, it is also possible to use manganese dioxides containing atleast one element selected from among elements other than manganese andalkali metal elements, for example, elements in Groups 2, 3, 4, 5, 6, 8,9, 10, 11, 12, 13, 14 and 15 of the periodic table. Among them,manganese dioxides containing at least one element selected from alkaliearth metals, Sc, Y, Zr, V, Nb, Ta, Cr, Mo, W, Zn, Ga, In, Ge, Sn, Pband Bi are preferred because these are excellent in reaction activity ofACH hydration and selectivity of HBD. Particularly preferred aremanganese dioxides containing at least one element selected from V, Snand Bi because these are particularly excellent in reaction activity ofACH hydration and selectivity of HBD. It is also possible to suitablyuse manganese dioxides containing two or more elements.

As the method for adding these elements to manganese dioxide, any methodsuch as impregnation, adsorption, kneading and coprecipitation may beused. As the element source, water-soluble compounds such as nitratesand sulfates, and oxides, hydroxides, etc. can be used. For example,when preparing a vanadium-containing manganese oxide catalyst, as thevanadium source, water-soluble salts such as vanadium sulfate andvanadium chloride are preferably used, and vanadium sulfate isparticularly preferably used. When preparing a tin-containing manganeseoxide catalyst, as the tin source, water-soluble salts such as tinsulfate and tin chloride are preferably used, and tin sulfate isparticularly preferably used. When preparing a bismuth-containingmanganese oxide, as the bismuth source, water-soluble salts such asbismuth sulfate and bismuth nitrate can be used, but bismuth oxide isparticularly preferably used.

The amount of these elements contained in manganese dioxide is notparticularly limited, but when represented by the atomic ratio relativeto manganese element, elements/manganese contained in manganese dioxideis preferably 0.001 to 0.1, and particularly preferably 0.002 to 0.04.

In the present invention, a particularly preferred catalyst composedmainly of manganese oxide comprises a compound represented bycomposition formula:Mn_(a)K_(b)M_(c)O_(d)wherein: Mn represents manganese; K represents potassium; O representsoxygen; M represents at least one element selected from V, Sn and Bi;and regarding the atomic ratio of each element, when a=1, b is 0.005 to0.5, c is 0.001 to 0.1, and d is 1.7 to 2.0. Further, in addition to theabove-described compound, hydrated water may also be contained in thecatalyst composed mainly of manganese oxide.

In the HBD production of the present invention, the manganese oxideprepared according to the above-described method can be molded into aform of pellet or tablet to be used as a fixed bed catalyst or moldedinto a form of granule or microsphere to be used as a slurry bedcatalyst, and can be filled or dispersed in the reaction regions to beused for hydration of ACH. Further, a molded product obtained by using acompound having plasticity and bonding capability such as silica andclay mineral can also be used.

The method for producing the raw material ACH which can be used for theHBD production of the present invention is not particularly limited. Forexample, it is possible to use the ACH which is synthesized from acetoneand hydrocyanic acid obtained by dehydration reaction of formamide.Further, it is also possible to use the ACH which is synthesized fromacetone and hydrocyanic acid obtained by a reaction between methane andammonia as in the case of the Andrussow oxidation or the BMA process,the ACH which is synthesized from acetone and hydrocyanic acid obtainedby ammoxidation of propane, or the like. In general, synthesis of ACH bymeans of a reaction between hydrocyanic acid and acetone isquantitatively progressed in the presence of a catalyst such as analkali metal compound, amine and basic ion exchange resin, and ACH isobtained with a high yield. In the HBD production of the presentinvention, it is possible to use ACH synthesized with using thesecatalysts. In this case, ACH can be used after subjected to distillationand purification, and can also be used without distillation andpurification.

In the present invention, the reaction temperature of hydration of ACHis preferably 20 to 120° C., and particularly preferably 30 to 90° C.The reaction pressure may be under reduced pressure or under highpressure, but is preferably 0.01 to 1.0 MPa, and particularly preferably0.05 to 0.5 MPa. As the ACH retention time in each reaction region, anoptimum value is selected depending on the reaction method and catalystactivity, but usually, it is preferably 30 seconds to 15 hours, morepreferably 15 minutes to 10 hours, and particularly preferably 30minutes to 5 hours.

In the HBD production of the present invention, pH of the reactionregion supply liquid (C) supplied to the reaction regions is preferablyadjusted to 4 or more, and particularly preferably adjusted to 4 to 8.The adjustment of pH can be carried out by cyclically supplying thereaction liquid as explained above, and in addition, amines disclosed inJapanese Laid-Open Patent Publication No. H11-335341 and oxides andhydroxides of alkali metals disclosed in Japanese Laid-Open PatentPublication No. H02-193952 can be used.

The reaction apparatus for the HBD production of the present inventionis a reaction apparatus for producing α-hydroxyisobutyric acid amide byhydration of acetone cyanohydrin in the presence of a catalyst composedmainly of manganese oxide, wherein the reaction apparatus has at leasttwo reaction regions connected in series and further has:

-   (a) a piping for supplying a reaction raw material liquid containing    the acetone cyanohydrin dividedly to a first reaction region (I) and    at least one reaction region other than the first reaction region in    the reaction apparatus; and/or-   (b) a piping for cyclically supplying at least a portion of a    reaction liquid withdrawn from at least one reaction region to the    first reaction region (I) in the reaction apparatus,-   and wherein the reaction apparatus further has a piping for    supplying an oxidizing agent to at least one reaction region.

The reaction apparatus for the HBD production of the present inventionpreferably has a piping for cyclically supplying a portion of thereaction liquid withdrawn from at least one reaction region to at leastone reaction region other than the first reaction region. In this case,the embodiment of the piping for cyclically supplying the reactionliquid withdrawn from the aforementioned reaction region to the reactionregion is not particularly limited. For example, it is possible toemploy an embodiment in which the piping for cyclically supplying thereaction liquid withdrawn from the reaction region is independentlyconnected to the reaction region, or an embodiment in which the reactionliquid is mixed with the reaction raw material liquid and the diluentsuch as water, acetone and HBD in a raw material preparation tank,storage tank or the like before being supplied to the reaction regionand these materials are simultaneously supplied to the reaction regionwith one piping, or an embodiment in which the piping for cyclicallysupplying the reaction liquid withdrawn from the reaction region isconnected to a piping for supplying the reaction raw material liquid andthe diluent such as water, acetone and HBD to the reaction region or apiping for connecting reaction regions. Further, it is also possible toprovide the reaction region in the middle of the circulation line forcyclically supplying the reaction liquid. Moreover, the reactionapparatus may have at least one circulation loop composed of: at leastone reaction region (II) other than the first reaction region; at leastone reaction region (IV) from which the reaction liquid is withdrawn inorder to cyclically supply the reaction liquid to the reaction region;and a piping for connecting the former reaction region and the latterreaction region, and it is more preferred that both the reaction region(II) and the reaction region (IV), which constitute at least onecirculation loop (V) among said circulation loop, are placed at aposition nearer to the outlet of the reaction apparatus of the presentinvention (downstream) compared to a reaction region that is nearest tothe inlet of the reaction apparatus among the at least one reactionregion from which the reaction liquid is withdrawn in order tocyclically supply the reaction liquid to the first reaction region (I).Alternatively, when the reaction liquid is withdrawn from a plurality ofreaction regions in order to cyclically supply the reaction liquid tothe reaction region (I), it is even more preferred that both thereaction region (II) and the reaction region (IV), which constitute atleast one circulation loop (V) among said circulation loop, are providedat a position nearer to the outlet of the reaction apparatus(downstream) compared to a reaction region in which the integratedquantity of the reaction liquid withdrawn from the respective reactionregions exceeds 50% of the total amount of the reaction liquidcyclically supplied to the reaction region (I) for the first time, andit is most preferred that both the reaction region (II) and the reactionregion (IV), which constitute at least one circulation loop (V) amongsaid circulation loop, are provided at a position nearer to the outletof the reaction apparatus (downstream) compared to all the reactionregions from which the reaction liquid is withdrawn in order tocyclically supply the reaction liquid to the first reaction region (I).

Regarding the arrangement of the reaction region (II) and the reactionregion (IV) which constitute the circulation loop (V), it is preferredthat the reaction region (IV) is provided at a position nearer to theoutlet of the reaction apparatus of the present invention compared tothe reaction region (II). Alternatively, it is preferred that thereaction region (II) is identical to the reaction region (IV).

The reaction apparatus for the HBD production of the present inventionpreferably has a piping for supplying a diluent containing at least onecompound selected from water, acetone, HBD and formamide to at least onereaction region. The reaction apparatus more preferably has a piping forsupplying the diluent to the reaction region to which ACH is dividedlysupplied. In this case, the embodiment of the piping for supplying thediluent to the reaction region is not particularly limited. For example,it is possible to employ an embodiment in which the piping for supplyingthe diluent is independently connected to the reaction region, or anembodiment in which the diluent is mixed with the reaction raw materialliquid in a raw material preparation tank before being supplied to thereaction region and these materials are simultaneously supplied to thereaction region with one piping, or an embodiment in which the pipingfor supplying the diluent is connected to the piping for supplying thereaction raw material liquid to the reaction region.

The reaction apparatus for the HBD production of the present inventionhas a piping for supplying an oxidizing agent to at least one reactionregion. In this case, the embodiment of the piping for supplying theoxidizing agent to the reaction region is not particularly limited.

In the reaction apparatus for the HBD production of the presentinvention, it is preferred that an equipment for withdrawing theoxidizing agent is connected to the first reaction region (I) and/or aposition between at least one reaction region other than the firstreaction region and another reaction region, or the the first reactionregion (I) and/or the middle portion of at least one reaction regionother than the first reaction region.

<Specific Examples of Reaction Apparatus and Production Method forCarrying out the Present Invention>

Hereinafter, specific examples of a preferred reaction apparatus andproduction method for carrying out the present invention (combinationmethod) will be described. FIG. 1 is a process flow diagram showing anexample of a reaction apparatus for the HBD production composed of threereactors, i.e., a first reactor 1 a, a second reactor 1 b and a thirdreactor 1 c.

To the first reactor 1 a, the second reactor 1 b and the third reactor 1c, a first reaction region 2 a, a second reaction region 2 b and a thirdreaction region 2 c, in each of which a catalyst is filled, are providedrespectively. To the first reactor 1 a, a supply line 10 a of reactionliquid to be supplied to the inlet of the first reaction region and anoxidizing agent supply line 4 a are connected, and to the opposite sideacross the first reaction region 2 a, an outflow line 11 a of reactionliquid flowing out from the outlet of the first reaction region and anoxidizing agent withdrawing line 5 a are connected. To the secondreactor 1 b, a supply line 10 b of reaction liquid to be supplied to theinlet of the second reaction region and an oxidizing agent supply line 4b are connected, and to the opposite side across the second reactionregion 2 b, an outflow line 11 b of reaction liquid flowing out from theoutlet of the second reaction region and an oxidizing agent withdrawingline 5 b are connected. To the third reactor 1 c, a supply line 10 c ofreaction liquid to be supplied to the inlet of the third reaction regionand an oxidizing agent supply line 4 c are connected, and to theopposite side across the third reaction region 2 c, an outflow line 11 cof reaction liquid flowing out from the outlet of the third reactionregion and an oxidizing agent withdrawing line 5 c are connected.

3 a and 3 b are a supply line of reaction raw material liquid containingACH. 6 a and 6 b are a circulation line for returning the reactionliquid from the outlet of the reaction region to the inlet of theoriginal reaction region. 7 is a cooler for cooling the reaction liquidcirculated from the outlet of the reaction region. 8 is a pump fordelivering the reaction liquid from the outlet of the reaction region. 9is a heater for heating the reaction raw material liquid to apredetermined temperature. 12 a and 12 b are liquid reservoirs fortemporarily storing the reaction liquid from the outlet of the reactionregion.

An example of the method for producing HBD using the reaction apparatusin FIG. 1 will be described. The reaction raw material liquid containingACH is dividedly supplied from the reaction raw material liquid supplylines 3 a and 3 b via the heaters 9. From 3 a, a mixed raw materialobtained by adding at least acetone to a mixture of ACH and water issupplied as the reaction raw material liquid. Meanwhile, from 3 b, ACHalone as a raw material, or a mixed raw material obtained by adding atleast water and/or acetone to ACH is supplied as the reaction rawmaterial liquid. Note that in FIG. 1, reaction raw materials consistingof ACH, water, acetone, etc. are mixed together and then the mixture issupplied to the reactors using 3 a and 3 b, but these components mayalso be respectively supplied to the reactors using independent supplylines.

The ACH concentration and the water concentration in the reaction rawmaterial liquid supplied from 3 a are not particularly limited, but froma practical viewpoint, it is preferred that the ACH concentration is 30to 60% by weight and that the water concentration is 70 to 40% byweight, and it is particularly preferred that the ACH concentration is35 to 50% by weight and that the water concentration is 65 to 50% byweight. Further, the acetone concentration in the reaction raw materialliquid is not particularly limited, but it is preferably 3 to 20% byweight, and more preferably 5 to 15% by weight. Meanwhile, the ACHconcentration and the water concentration in the reaction raw materialliquid supplied from 3 b are not particularly limited, and it ispreferred that the ACH concentration is 30 to 100% by weight and thatthe water concentration is 0 to 50% by weight. Further, the acetoneconcentration in the reaction raw material liquid is preferably 0 to 20%by weight.

The reaction raw material liquid containing ACH supplied from 3 a and 3b is mixed with the reaction liquid from the outlet of the reactionregion circulated from 6 a and 6 b, and the mixture is supplied to therespective reactors via 10 a and 10 b. As previously described, theratio of the supply rate of the reaction liquid from the outlet of thereaction region circulated from 6 a and 6 b (X) to the differencebetween the supply rate of the whole reaction liquid supplied to thereaction regions 2 a and 2 b (Y) and the supply rate of the reactionliquid cyclically supplied from 6 a and 6 b (X) ((X)/((Y)−(X))), i.e.,the circulation ratio is not particularly limited, but when representedby the volume velocity ratio, it is preferably 0.5 to 50, andparticularly preferably 1 to 20. Note that in FIG. 1, the reaction rawmaterial liquid is mixed with the reaction liquid from the outlet of thereaction region and then the mixture is supplied to the reactors via 10a and 10 b, but these liquids may also be respectively supplied to thereactors using independent supply lines.

Hydration of ACH is performed with the previously described reactiontemperature and reaction pressure. The method for controlling thereaction temperature of hydration of ACH is not particularly limited.For example, it is possible to use: a method in which a heating mediumor a hot-water-circulated jacket is provided around the reaction regionfilled with the catalyst; a method in which a heat transfer coil isprovided to the inside of the reaction region; and a method in which theheat-retention means for preventing heat dissipation is provided to theoutside of the reaction region and the heater 9 or cooler 7 is providedto the lines for flow of the reaction raw material liquid and thereaction liquid from the outlet of the reaction region (3 a, 6 a, 13 a,3 b, 6 b and 13 b in FIG. 1) to adjust the temperature of the reactionliquid. Note that FIG. 1 shows an example in which the heater 9 and thecooler 7 are provided, but it is not required to provide the heater 9and the cooler 7 when the liquid temperature of the mixture of thereaction raw material liquid and the reaction liquid from the outlet ofthe reaction region can be controlled to a predetermined temperature forperforming hydration of ACH without use of the heater 9 and the cooler7. From a practical viewpoint, it is preferred to provide the heater 9and the cooler 7 to control the reaction temperature because it becomeseasier to operate the reaction apparatus stably.

As previously described, in order to prevent the catalyst composedmainly of manganese oxide from being reduced and deactivated, anoxidizing agent is supplied from the oxidizing agent supply lines 4 a, 4b and 4 c. When using an oxygen-containing gas as the oxidizing agent,the oxygen-containing gas is supplied from the oxidizing agent supplylines 4 a, 4 b and 4 c, and the gas whose oxygen concentration hasdecreased is withdrawn from the oxidizing agent withdrawing lines 5 a, 5b and 5 c. As the gas to be supplied from 4 a, 4 b and 4 c, a freshoxygen-containing gas may be used, or a gas obtained by mixing the gaswhose oxygen concentration has decreased withdrawn from 5 a, 5 b and 5 cwith a fresh oxygen-containing gas to provide a sufficient oxygenconcentration may be used. When the gas withdrawn from 5 a, 5 b and 5 cstill has a sufficient oxygen concentration, it may be directly suppliedto the original reaction region or other reaction regions via 4 a, 4 band 4 c.

A portion of ACH supplied from the reaction liquid supply line 10 abecomes HBD by hydration in the first reaction region 2 a. The reactionliquid from the outlet of the reaction region flowing out from the firstreaction region 2 a is passed through the outflow line 11 a andtemporarily stored in the liquid reservoir 12 a. After that, it isdividedly supplied to 6 a as a circulation liquid to the first reactionregion and to 13 a as a supply liquid to the second reaction region at apredetermined ratio. Usually, the supply rate of the liquid to thesecond reaction region is the same as the supply rate of the reactionraw material liquid supplied from 3 a.

The supply liquid to the second reaction region delivered from 13 a isjoined together with the reaction raw material liquid supplied from 3 band the circulation liquid from the outlet of the second reaction regiondelivered from 6 b, and the mixture is supplied to the second reactionregion 2 b via the reaction liquid supply line 10 b. In the secondreaction region, ACH supplied from 3 b and ACH circulated from 6 b areconverted into HBD, and therefore, the HBD concentration in the reactionliquid from the outlet of the second reaction region is higher than theHBD concentration in the reaction liquid from the outlet of the firstreaction region. The reaction liquid from the outlet of the reactionregion flowing out from the second reaction region 2 b is passed throughthe outflow line 11 b and temporarily stored in the liquid reservoir 12b. After that, it is dividedly supplied to 6 b as a circulation liquidto the second reaction region and to 13 b as a supply liquid to thethird reaction region at a predetermined ratio. Usually, the supply rateof the liquid to the third reaction region is the same as the sum of thesupply rate of the reaction raw material liquid supplied from 3 b andthe supply rate of the liquid to the second reaction region suppliedfrom 13 a.

The supply liquid to the third reaction region delivered from 13 b issupplied to the third reaction region 2 c via 10 c. In the thirdreaction region 2 c, a major part of ACH in the reaction liquid isconverted into HBD, and finally, a solution of HBD having aconcentration of 40% by weight or more is obtained and is delivered from11 c to an apparatus for the next process or a storage apparatus.

The process flow diagram of the preferred reaction apparatus forcarrying out the present invention is not limited to FIG. 1. Forexample, there are various methods such as: a method in which aplurality of reaction regions are provided in one reactor and a reactionliquid circulation line is provided to each of them (FIG. 2); a methodin which the reaction liquid is withdrawn from the middle of onereaction region, the liquid temperature is adjusted using a heatexchanger and then the liquid is returned to the reaction region (FIG.3); and a method in which the circulation liquid is returned to aplurality of areas in one reaction region (FIG. 4).

EXAMPLES

Hereinafter, the present invention will be more specifically describedby way of examples and comparative examples. However, the scope of thepresent invention is not limited by these examples.

Preparation of Catalyst

To a solution obtained by dissolving 62.92 g (0.398 mol) of potassiumpermanganate in 220 ml of water, a solution obtained by dissolving 54.43g (0.322 mol) of manganese sulfate monohydrate in 215 ml of water andfurther mixing it with 99.54 g (0.964 mol) of concentrated sulfuric acidwas added by pouring rapidly with stirring at 75° C. The mixture wascontinuously stirred at 70° C. for 2 hours and then further stirred at90° C. for 4 hours to be matured. After that, a solution obtained bysuspending 1.90 g (0.007 mol) of bismuth (III) oxide in 440 ml of waterwas added thereto by pouring rapidly. The mixture was stirred at roomtemperature for 30 minutes, and then the obtained precipitate wasfiltered and washed 4 times with 200 ml of water, thereby obtaining aprecipitated cake.

The obtained cake was molded using an extruder (cylinder diameter: 35mmΦ, nozzle diameter: 1.5 mmΦ×24 holes, rate of hole area: 4.4%, oilpressure type), and it was dried at 110° C. for 15 hours using aventilation dryer, thereby obtaining about 60 g of a pellet-type moldedcatalyst having a diameter of about 1 mmφ and a length of 5 to 10 mm.The content of metal components of the obtained catalyst was measured,and in each case, bismuth/potassium/manganese was 0.01/0.09/1.0 (atomicratio).

Hydration of ACH

Example 1

Hydration of ACH was performed using a reaction apparatus shown in FIGS.5. 1 a, 1 b and 1 c are a reactor made of glass having an inner diameterof about 18 mmφ equipped with a jacket (a first reactor, a secondreactor and a third reactor, respectively). 2 a is a first reactionregion, and it was filled with 16 g of the catalyst prepared accordingto the above-described method. 2 b is a second reaction region, and itwas filled with 16 g of the catalyst prepared according to theabove-described method. 2 c is a third reaction region, and it wasfilled with 8 g of the catalyst prepared according to theabove-described method. 3 a is a first reaction raw material liquidsupply line, and the first reaction raw material liquid consisting of55.5% by weight of pure water, 9.5% by weight of acetone and 35% byweight of ACH was supplied at a rate of 14.8 g/hr. 3 b is a secondreaction raw material liquid supply line, and the second reaction rawmaterial liquid consisting of 17% by weight of pure water, 13% by weightof acetone and 70% by weight of ACH was supplied at a rate of 2.47 g/hr.The ratio of ACH supplied to the first reaction raw material liquidsupply line to all the supplied ACH was 75% by weight. 4 a is a firstoxidizing agent supply line, and an oxygen-containing gas consisting of9% oxygen and 91% nitrogen on the volume basis was supplied at a rate of26.7 ml/hr. The oxygen-containing gas supplied from 4 a was passedthrough the first reaction region 2 a to be led to the outlet of thefirst reactor (outflow line) 11 a and to a reaction liquid pool (liquidreservoir) 12 a at the outlet of the first reaction region, and wascompletely withdrawn from a first oxidizing agent withdrawing line 5 ato the outside of the system. 4 b is a second oxidizing agent supplyline, and an oxygen-containing gas consisting of 9% oxygen and 91%nitrogen on the volume basis was supplied at a rate of 26.7 ml/hr. Theoxygen-containing gas supplied from 4 b was passed through the secondreaction region 2 b, the outlet of the second reactor (outflow line) 11b, a reaction liquid pool (liquid reservoir) 12 b at the outlet of thesecond reaction region and a liquid supply line 10 c at the inlet of thethird reaction region to be led to the third reactor 1 c, and furtherpassed through the third reaction region 2 c and then withdrawn from theoutlet of the third reactor (outflow line) 11 c to the outside of thesystem together with the reaction liquid at the outlet of the thirdreaction region. The whole reaction liquid from the outlet of the firstreaction region flowing out from the outlet of the first reactor 11 awas temporarily collected into the reaction liquid pool 12 a at theoutlet of the first reaction region. A portion of the collected reactionliquid was delivered to a liquid supply line 10 a at the inlet of thefirst reaction region via a circulation line 6 a for the reaction liquidfrom the outlet of the first reaction region using a liquid deliverypump 8 a at a rate of 120 g/hr. The circulation ratio of the reactionliquid circulated to the inlet of the first reaction region was 8.1. Thereaction liquid pool 12 a at the outlet of the first reaction region isequipped with a liquid level sensor, and the reaction liquid flowing outfrom the outlet of the first reactor 11 a at a rate higher than 120 g/hrwas delivered to the second reactor 1 b via a liquid delivery line 13 ato the second reaction region while controlling the liquid level of thereaction liquid pool 12 a at the outlet of the first reaction region tobe constant by means of the liquid level sensor and a liquid deliverypump 8 t. The supply rate of the liquid delivered from the liquiddelivery pump 8 t was 14.8 g/hr. 12 b is a reaction liquid pool (liquidreservoir) at the outlet of the second reaction region. The wholereaction liquid flowing out from the outlet of the second reactor(outflow line) 11 b was temporarily collected into a reaction productliquid pool 12 b at the outlet of the second reaction region. A portionof the collected reaction liquid was delivered to a liquid supply line10 b at the inlet of the second reaction region via a circulation line 6b for the reaction liquid from the outlet of the second reaction regionusing a liquid delivery pump 8 b at a rate of 26.5 g/hr. The circulationratio of the reaction liquid circulated to the inlet of the secondreaction region was 1.5. The reaction liquid from the outlet of thesecond reaction region flowing out from the outlet of the second reactor11 b at a rate higher than 26.5 g/hr was overflowed from an openingprovided in the side surface of the reaction liquid pool 12 b at theoutlet of the second reaction region and delivered to the third reactor1 c via a liquid delivery tube (liquid delivery line) 13 b. Note thatthe oxygen-containing gas supplied from the second oxidizing agentsupply line was delivered to the third reactor 1 c from the same liquiddelivery tube 13 b. The reaction liquid from the outlet of the secondreaction region delivered to the third reactor 1 c was passed throughthe third reaction region 2 c and withdrawn from the outlet of the thirdreactor 11 c to the outside of the system. In each of the reactionregions 2 a, 2 b and 2 c, the reaction liquid ran down on the surface ofthe catalyst, and in each case, the catalyst layer was held in a stateof so-called “trickle bed”. The liquid in the reaction liquid pool 12 aat the outlet of the first reaction region, the liquid in the reactionliquid pool 12 b at the outlet of the second reaction region and theliquid at the outlet of the third reactor 11 c were analyzed by HPLC,and the ACH concentration was analyzed. The reaction temperature wassuitably adjusted so that the ACH concentration at the outlet of thethird reactor 11 c did not exceed 1% by weight. The amount of theproduction of HBD as the target product and time-dependent change in theconversion of ACH as the raw material are shown in Table 1, and the ACHconcentration in liquids at inlets and outlets of the reactors 1 a, 1 band 1 c calculated from analysis values and liquid flow rates is shownin Table 2. Note that at each point, the yield of HBD as the targetproduct at the outlet of the third reactor 11 c was 95% or more.Further, the manganese concentration in the liquid in the reactionliquid pool 12 a at the outlet of the first reaction region was measuredusing a polarized Zeeman atomic absorption spectrometer (manufactured byHitachi High-Technologies, Z-2000). The results are shown in Table 2.

At the point when the reaction temperature for maintaining the ACHconcentration at the outlet of the third reactor 11 c at 1% or lessbecame 56° C. or higher, the reaction was terminated. The period of theoperation was 750 days, and the total amount of the production of HBDwas 3717.8 g per 1 g of the catalyst.

TABLE 1 HBD production Reaction amount temperature ACH conversion % Timedays g-HBD/g-cat ° C. 11a 11b 11c 54 250.4 47.5 84.4 93.9 97.9 3001432.5 48.5 82.6 94.5 98.6 501 2432.2 48 77.7 93.6 98.0 600 2912.1 4975.2 93.1 97.7 750 3717.8 56 74.3 92.5 97.4

TABLE 2 Mn concen- tration Time ACH concentration % ppm days 3a 3b 10a10b 10c 11a 11b 11c 12a 54 35.0 70 8.5 7.2 2.4 5.3 2.4 0.8 1.1 300 35.070 9.6 7.5 2.2 6.5 2.2 0.6 0.6 501 35.0 70 11.3 8.4 2.6 8.5 2.6 0.8 0.9600 35.0 70 12.4 8.9 2.8 9.7 2.8 0.9 1.9 750 35.0 70 12.9 9.3 3.0 10.33.0 1.1 1.3

Example 2

Hydration of ACH was performed under the same reaction conditions asthose in Example 1, except that a reaction raw material liquidconsisting of 50% by weight of pure water, 10% by weight of acetone and40% by weight of ACH was supplied from the first reaction raw materialliquid supply line 3 a at a rate of 17.28 g/hr and no raw material wassupplied from the second reaction raw material liquid supply line 3 b.The amount of the production of HBD as the target product andtime-dependent change in the conversion of ACH as the raw material areshown in Table 3, and the ACH concentration in liquids at inlets andoutlets of the reactors 1 a, 1 b and 1 c calculated from analysis valuesand liquid flow rates is shown in Table 4. Note that at each point, theyield of HBD as the target product at the outlet of the third reactor(outflow line) 11 c was 95% or more. Further, the manganeseconcentration in the liquid in the reaction liquid pool (liquidreservoir) 12 a at the outlet of the first reaction region was measuredusing a polarized Zeeman atomic absorption spectrometer (manufactured byHitachi High-Technologies, Z-2000). The results are shown in Table 4.The Mn concentration in the reaction liquid at the outlet of the firstreaction region was 1.8 to 2.0 ppm.

On day 102 of the reaction, the reaction temperature required formaintaining the ACH concentration at the outlet of the third reactor 11c at 1% or less was 47.5° C., and at that point, the total amount of theproduction of HBD was 483.8 g per 1 g of the catalyst.

TABLE 3 HBD production Reaction amount temperature ACH conversion % Timedays g-HBD/g-cat ° C. 11a 11b 11c 55 259.5 47.0 75.5 94.5 98.4 102 483.847.5 74.4 94.7 98.2

TABLE 4 Mn concentration Time ACH concentration % ppm days 3a 10a 10b10c 11a 11b 11c 12a 55 40.0 13.6 5.2 2.2 9.8 2.2 0.6 2.0 102 40.0 14.05.3 2.1 10.3 2.1 0.7 1.8

Example 3

Hydration of acetone cyanohydrin was performed using a reactionapparatus shown in FIG. 6. 1 a, 1 b and 1 c are a reactor made of glasshaving an inner diameter of about 18 mmφ equipped with a jacket (a firstreactor, a second reactor and a third reactor, respectively). 2 a is afirst reaction region, and it was filled with 8 g of the catalystprepared according to the above-described method. 2 b is a secondreaction region, and it was filled with 8 g of the catalyst preparedaccording to the above-described method. 2 c is a third reaction region,and it was filled with 8 g of the catalyst prepared according to theabove-described method. 3 a is a raw material supply tube (supply line),and the first raw material consisting of 50.0% by weight of pure water,10.0% by weight of acetone and 40% by weight of acetone cyanohydrin(referred to as ACH in Tables) was supplied at a rate of 12.0 g/hr. 4 ais an oxidizing agent supply tube (supply line), and as theoxygen-containing gas, air was supplied at a rate of 16.0 ml/hr. Theoxygen-containing gas supplied from 4 a was passed through the firstreaction region 2 a and further passed through the outlet of the reactor(outflow line) 11 a, a first reaction liquid pool (liquid reservoir) 12a, a liquid delivery tube (liquid delivery line) 13 a, the secondreactor 1 b, the second reaction region 2 b, the outlet of the reactor(outflow line) 11 b, a second reaction liquid pool (liquid reservoir) 12b, a liquid delivery tube (liquid delivery line) 13 b, the third reactor1 c and the third reaction region 2 c, and discharged together with thereaction liquid from the outlet of the reactor (outflow line) 11 c tothe outside of the system. 12 a is the first reaction liquid pool. Thewhole reaction liquid flowing out from the first reactor 1 a wastemporarily collected into the first reaction liquid pool 12 a anddelivered to a reaction liquid supply tube (supply line) 10 a via areaction liquid circulation line 6 a using a liquid delivery pump 8 a ata rate of 120 g/hr. The reaction liquid flowing out from the firstreactor 1 a at a rate higher than 120 g/hr was overflowed from anopening provided in the side surface of the first reaction liquid pool12 a and delivered to the second reactor 1 b via a liquid delivery tube13 a. The reaction liquid delivered from a reaction liquid supply tube10 b to the second reactor 1 b was passed through the second reactionregion 2 b and delivered from the outlet of the reactor 11 b to thesecond liquid pool 12 b to be temporarily collected. The reaction liquidwas delivered from the second liquid pool 12 b to a reaction liquidsupply tube 10 b via a reaction liquid circulation line 6 b using aliquid delivery pump 8 b at a rate of 120 g/hr. The reaction liquidflowing out from the second reactor 1 b at a rate higher than 120 g/hrwas overflowed from an opening provided in the side surface of thesecond reaction liquid pool 12 b and delivered to the third reactor 1 cvia a liquid delivery tube 13 b. The reaction liquid delivered to thethird reactor 1 c was passed through the third reaction region 2 c anddischarged from the outlet of the third reactor 11 c to the outside ofthe system. In each of the reaction regions 2 a, 2 b and 2 c, thereaction liquid ran down on the surface of the catalyst, and in eachcase, the catalyst layer was held in a state of so-called “trickle bed”.The reaction liquid in the first reaction liquid pool 12 a, the reactionliquid in the second reaction liquid pool 12 b and the reaction liquidat the outlet of the third reactor 11 c were analyzed by HPLC, and theacetone cyanohydrin concentration was analyzed. The reaction temperaturewas suitably adjusted so that the acetone cyanohydrin concentration atthe outlet of the third reactor 11 c did not exceed 1% by weight. Theamount of the production of α-hydroxyisobutyric acid amide (HBD) as thetarget product and time-dependent change in the conversion of acetonecyanohydrin as the raw material are shown in Table 5, and the acetonecyanohydrin concentration in reaction liquids at the inlets and outletsof the reactors 1 a, 1 b and 1 c calculated from analysis values andreaction liquid flow rates is shown in Table 6. Note that at each point,the yield of α-hydroxyisobutyric acid amide as the target product at theoutlet of the third reactor 11 c was 95% or more. Further, the manganeseconcentration in the reaction liquid in the first reaction liquid pool12 a was measured using an atomic absorption spectrometer (manufacturedby Hitachi High-Technologies, Z-2000). The results are shown in Table 6.

At the point when the reaction temperature for maintaining the acetonecyanohydrin concentration at the outlet of the third reactor 11 c at 1%or less became 56° C. or higher, the reaction was terminated. The totalamount of the production of α-hydroxyisobutyric acid amide was 2261.5 gper 1 g of the catalyst.

TABLE 5 HBD production Reaction amount temperature ACH conversion % Timedays g-HBD/g-cat ° C. 11a 11b 11c 50 278.3 49.0 69.2 90.0 97.8 152 844.950.5 63.7 88.5 97.8 301 1679.7 50.5 64.6 90.3 98.1 405 2261.5 56.0 56.682.7 97.6

TABLE 6 Mn concentration Time ACH concentration % ppm days 3a 10a 10b10c 11a 11b 11c 12a 50 40.0 14.9 4.8 4.0 12.3 4.0 0.9 3.6 152 40.0 16.95.5 4.6 14.5 4.6 0.9 2.7 301 40.0 16.5 4.8 3.9 14.2 3.9 0.8 2.0 405 40.019.4 7.9 6.9 17.4 6.9 1.0 4.5

The present invention also includes the following embodiments:

-   <1> A method for producing α-hydroxyisobutyric acid amide by    hydration of acetone cyanohydrin in the presence of a catalyst    composed mainly of manganese oxide using a reaction apparatus in    which at least two reaction regions are connected in series, wherein    the method comprises at least one step selected from:

a step (A) of supplying a reaction raw material liquid containingacetone cyanohydrin to the first reaction region (I) and at least onereaction region (II) other than the first reaction region in thereaction apparatus; and

a step (B) of cyclically supplying at least a portion of a reactionliquid withdrawn from at least one reaction region (III) to the firstreaction region (I) in the reaction apparatus.

-   <2> The method for producing α-hydroxyisobutyric acid amide    according to item <1>, wherein the number of the reaction regions    connected in series is 7 or less.-   <3> The method for producing α-hydroxyisobutyric acid amide    according to item <1> or <2>, wherein the number of the reaction    regions to which the reaction raw material liquid containing acetone    cyanohydrin is supplied in the step (A) is 5 or less.-   <4> The method for producing α-hydroxyisobutyric acid amide    according to any one of items <1> to <3>, wherein the molar ratio    between water and acetone cyanohydrin in a reaction region supply    liquid (C) supplied to the reaction regions is such that the amount    of water is 1 to 200 mol relative to 1 mol of acetone cyanohydrin.-   <5> The method for producing α-hydroxyisobutyric acid amide    according to item <4>, wherein acetone is contained in the reaction    region supply liquid (C).-   <6> The method for producing α-hydroxyisobutyric acid amide    according to item <4> or <5>, wherein α-hydroxyisobutyric acid amide    is contained in the reaction region supply liquid (C).-   <7> The method for producing α-hydroxyisobutyric acid amide    according to any one of items <1> to <6>, wherein the ratio of the    acetone cyanohydrin in the total amount of the reaction region    supply liquid (C) is 25% by weight or less.-   <8> The method for producing α-hydroxyisobutyric acid amide    according to any one of items <1> to <7>, wherein the acetone    cyanohydrin concentration in the reaction raw material liquid is 30%    by weight or more.-   <9> The method for producing α-hydroxyisobutyric acid amide    according to any one of items <1> to <8>, wherein in the step (B),    at least a portion of the reaction liquid withdrawn from the at    least one reaction region (III) is further cyclically supplied to    the at least one reaction region (II) other than the first reaction    region.-   <10> The method for producing α-hydroxyisobutyric acid amide    according to any one of items <1> to <9>, wherein an oxidizing agent    is supplied to the at least one reaction region (III) in the    reaction apparatus.-   <11> The method for producing α-hydroxyisobutyric acid amide    according to any one of items <1> to <10>, wherein the oxidizing    agent is supplied to all the reaction regions in the reaction    apparatus.-   <12> The method for producing α-hydroxyisobutyric acid amide    according to item <10> or <11>, wherein an oxygen atom-containing    gas is used as the oxidizing agent.-   <13> The method for producing α-hydroxyisobutyric acid amide    according to item <10> or <11>, wherein an oxygen-containing gas is    used as the oxidizing agent, and wherein the oxygen concentration in    the oxygen-containing gas is 2 to 50% by volume.-   <14> The method for producing α-hydroxyisobutyric acid amide    according to item <13>, wherein the gas in the reaction region is    exchanged by supplying a gas having a sufficient oxygen    concentration while withdrawing a gas having a reduced oxygen    concentration.-   <15> The method for producing α-hydroxyisobutyric acid amide    according to any one of items <12> to <14>, wherein a reaction    method is a trickle flow-type continuous reaction method.-   <16> The method for producing α-hydroxyisobutyric acid amide    according to any one of items <1> to <15>, wherein the catalyst    composed mainly of manganese oxide is manganese dioxide.-   <17> The method for producing α-hydroxyisobutyric acid amide    according to any one of items <1> to <16>, wherein the catalyst    composed mainly of manganese oxide comprises a compound represented    by composition formula: Mn_(a)K_(b)M_(c)O_(d)    wherein: Mn represents manganese; K represents potassium; O    represents oxygen; M represents at least one element selected from    V, Sn and Bi; and regarding the atomic ratio of each element, when    a=1, b is 0.005 to 0.5, c is 0.001 to 0.1, and d is 1.7 to 2.0.-   <18> The method for producing α-hydroxyisobutyric acid amide    according to item <17>, wherein the catalyst composed mainly of    manganese oxide further comprises hydrated water.-   <19> The method for producing α-hydroxyisobutyric acid amide    according to item <1>, which comprises the step (A) and the step    (B).-   <20> The method for producing α-hydroxyisobutyric acid amide    according to item <19>, wherein the ratio of the amount of acetone    cyanohydrin contained in the reaction raw material liquid supplied    to the first reaction region to the total amount of acetone    cyanohydrin contained in the reaction raw material liquid supplied    to the reaction apparatus in the step (A) is 50 to 98% by weight.-   <21> The method for producing α-hydroxyisobutyric acid amide    according to item <19> or <20>, wherein the circulation ratio in the    step (B) is 0.5 to 50 when represented by the volume velocity ratio.-   <22> A reaction apparatus for producing α-hydroxyisobutyric acid    amide by hydration of acetone cyanohydrin in the presence of a    catalyst composed mainly of manganese oxide, wherein the reaction    apparatus has at least two reaction regions connected in series and    further has:-   (a) a piping for supplying a reaction raw material liquid containing    acetone cyanohydrin to the first reaction region (I) and at least    one reaction region (II) other than the first reaction region in the    reaction apparatus; and/or-   (b) a piping for cyclically supplying at least a portion of a    reaction liquid withdrawn from at least one reaction region (III) to    the first reaction region (I) in the reaction apparatus.-   <23> The reaction apparatus according to item <22>, wherein in (b),    the reaction apparatus further has a piping for cyclically supplying    at least a portion of the reaction liquid withdrawn from the at    least one reaction region (III) to the at least one reaction    region (II) other than the first reaction region.-   <24> The reaction apparatus according to item <22> or <23>, which    further has a piping for supplying a diluent containing at least one    compound selected from water, acetone, α-hydroxyisobutyric acid    amide and formamide to the at least one reaction region (III).-   <25> The reaction apparatus according to any one of items <22> to    <24>, which further has a piping for supplying an oxidizing agent to    the at least one reaction region (III).-   <26> The reaction apparatus according to any one of items <22> to    <25>, wherein an equipment for withdrawing the oxidizing agent is    connected to the first reaction region (I) and/or a position between    the at least one reaction region (II) other than the first reaction    region and another reaction region, or the first reaction region (I)    and/or the middle portion of the at least one reaction region (II)    other than the first reaction region.

EXPLANATIONS OF LETTERS OR NUMERALS

-   1 a: first reactor-   1 b: second reactor-   1 c: third reactor-   2 a: first reaction region-   2 b: second reaction region-   2 c: third reaction region-   3 a, 3 b: reaction raw material liquid supply line-   4 a, 4 b, 4 c: oxidizing agent supply line-   5 a, 5 b, 5 c: oxidizing agent withdrawing line-   6 a, 6 b: circulation line-   7: cooler-   8: pump-   9: heater-   10 a, 10 b, 10 c: reaction liquid supply line-   11 a, 11 b, 11 c: reaction liquid outflow line-   12 a, 12 b: liquid reservoir-   13 a, 13 b: liquid delivery line

The invention claimed is:
 1. A method for producing α-hydroxyisobutyricacid amide by hydration of acetone cyanohydrin in the presence of acatalyst comprising manganese oxide using a reaction apparatus in whichtwo to seven reaction regions are connected in series, wherein themethod comprises: (B) cyclically supplying at least a portion of areaction liquid withdrawn from at least one reaction region to a firstreaction region (I) in the reaction apparatus; (b1) further cyclicallysupplying at least a portion of the reaction liquid withdrawn from atleast one reaction region to at least one reaction region other than thefirst reaction region (I), and (C) supplying at least a portion of areaction liquid withdrawn from at least one reaction region other thanthe first reaction region (I) to: i) at least one reaction region otherthan the first reaction region (I) which is the same as or upstream fromthe at least one reaction region other than the first reaction region(I) from which the reaction liquid is withdrawn, and ii) at least onereaction region other than the first reaction region (I) which isdownstream from the at least one reaction region other than the firstreaction region (I) from which the reaction liquid is withdrawn; whereinan oxidizing agent is supplied to at least one reaction region in thereaction apparatus, wherein the method further comprises supplying areaction raw material liquid containing the acetone cyanohydrin to thereaction apparatus, and wherein the concentration of the acetonecyanohydrin in the total amount of the reaction raw material liquid is30% by weight or more, and wherein the concentration of manganese elutedfrom the first reaction region (I) is less than or equal to 4.5 ppm. 2.A method for producing α-hydroxyisobutyric acid amide by hydration ofacetone cyanohydrin in the presence of a catalyst comprising manganeseoxide using a reaction apparatus in which two to seven reaction regionsare connected in series, wherein the method comprises: (A) supplying areaction raw material liquid containing the acetone cyanohydrindividedly to a first reaction region (I) and at least one reactionregion other than the first reaction region (I) in the reactionapparatus; (B) cyclically supplying at least a portion of a reactionliquid withdrawn from at least one reaction region to the first reactionregion (I) in the reaction apparatus; (b1) further cyclically supplyingat least a portion of the reaction liquid withdrawn from at least onereaction region to at least one reaction region other than the firstreaction region (I), and (C) supplying at least a portion of a reactionliquid withdrawn from at least one reaction region other than the firstreaction region (I) to: i) at least one reaction region other than thefirst reaction region (I) which is the same as or upstream from the atleast one reaction region other than the first reaction region (I) fromwhich the reaction liquid is withdrawn, and ii) at least one reactionregion other than the first reaction region (I) which is downstream fromthe at least one reaction region other than the first reaction region(I) from which the reaction liquid is withdrawn; wherein an oxidizingagent is supplied to at least one reaction region in the reactionapparatus, and wherein the concentration of the acetone cyanohydrin inthe total amount of the reaction raw material liquid is 30% by weight ormore, and wherein the concentration of manganese eluted from the firstreaction region (I) is less than or equal to 4.5 ppm.
 3. The method forproducing α-hydroxyisobutyric acid amide according to claim 1, whereinin at least a part of (b1) the reaction liquid withdrawn from the atleast one reaction region is cyclically supplied to a reaction regionthat is downstream from the at least one reaction region.
 4. The methodfor producing α-hydroxyisobutyric acid amide according to claim 3,wherein in at least a part of (b1) the reaction liquid withdrawn fromthe at least one reaction region is cyclically supplied downstream tothe final reaction region in the series of reaction regions.
 5. Themethod for producing α-hydroxyisobutyric acid amide according to claim1, wherein in (C) the portion of the reaction liquid withdrawn from atleast one reaction region other than the first reaction region iscyclically supplied to the same at least one reaction region other thanthe first reaction region.
 6. The method for producingα-hydroxyisobutyric acid amide according to claim 2, wherein the numberof the reaction regions to which the reaction raw material liquidcontaining acetone cyanohydrin is supplied in (A) is 5 or less.
 7. Themethod for producing α-hydroxyisobutyric acid amide according to claim1, wherein the reaction raw material liquid is supplied to two to sevenof the reaction regions of the reaction apparatus and wherein theconcentration of the acetone cyanohydrin in the reaction raw materialliquid is diluted to 25 wt % or less before being supplied to said twoto seven reaction regions using a diluent or a reaction liquid flowingout of or withdrawn from the reaction regions.
 8. The method forproducing α-hydroxyisobutyric acid amide according to claim 1, whereinan oxygen-containing gas is used as the oxidizing agent, and wherein theoxygen concentration in the oxygen-containing gas is 2 to 50% by volume.9. The method for producing α-hydroxyisobutyric acid amide according toclaim 8, wherein the oxygen-containing gas is supplied to the at leastone reaction region in the reaction apparatus while withdrawing a gashaving a reduced oxygen concentration from the at least one reactionregion in the reaction apparatus.
 10. The method for producingα-hydroxyisobutyric acid amide according to claim 1, wherein thecatalyst comprising manganese oxide is manganese dioxide.
 11. The methodfor producing α-hydroxyisobutyric acid amide according to claim 1,wherein the catalyst comprising manganese oxide comprises a compoundrepresented by composition formula: Mn_(a)K_(b)M_(c)O_(d) wherein: Mnrepresents manganese; K represents potassium; O represents oxygen; Mrepresents at least one element selected from the group consisting of V,Sn, and Bi; and regarding the atomic ratio of each element, a is 1, b is0.005 to 0.5, c is 0.001 to 0.1, and d is 1.7 to 2.0.